Search Results (632)

Anthocyanins are important flavonoid compounds with significant antioxidant activity and ornamental value in rice. In this study, using upland rice landrace 17SM-19 as the material, the anthocyanin content in leaves was determined at the one-(S1) and two-leaf stages (S2). The anthocyanin content at S1 (43.37 U/g) was significantly higher than that at S2 (16.54 U/g). With S1 considered the control, a total of 9865 differentially expressed genes (DEGs) were identified in the S2, among which 4702 were upregulated and 5163 were downregulated. Functional enrichment analyses revealed that these DEGs were significantly enriched in terms and pathways such as photosynthesis and ribosome. Screening of these DEGs identified 10 structural genes and four regulatory genes associated with anthocyanin biosynthesis. Quantitative real-time PCR verified the reliability of the transcriptome data. These results provide valuable clues for revealing the molecular mechanism underlying anthocyanin biosynthesis in rice leaves. Full article

Dendrobium huoshanense water extract (DHWE) exhibits hypoglycemic effects in streptozotocin-induced type 1 diabetic (STZ-T1D) rats. However, its regulatory impact on the gut microbiota of T1D rats remains largely unclear. In this study, metagenomic sequencing was employed to characterize alterations in the gut microbiota of STZ-T1D rats following DHWE intervention, aiming to explore associations between DHWE-mediated gut microbial changes and T1D-related phenotypes. The results showed that 1300 mg/kg·BW/day DHWE did not significantly affect gut microbial α-diversity (p > 0.05), but drove the β-diversity structure toward that of normal rats. Meanwhile, DHWE significantly reduced the Bacteroidota/Bacillota ratio (p < 0.05), Megamonas (p < 0.01), Megamonas funiformis (p < 0.01), and notably increased the relative abundances of Adlercreutzia (p < 0.01), Adlercreutzia equolifaciens (p < 0.01) in STZ-T1D rats. Furthermore, functional annotation revealed that DHWE enriched multiple metabolic pathways, including streptomycin biosynthesis, ansamycins biosynthesis, galactose metabolism, ether lipid metabolism, and caprolactam degradation. Collectively, these findings demonstrate that DHWE reshapes gut microbiota composition and function in STZ-T1D rats, offering new clues regarding how gut microbial changes may contribute to the modulatory effects of Dendrobium huoshanense in T1D conditions. Full article

Long non-coding RNAs (lncRNAs) have emerged as important regulatory molecules in plants, but their potential roles during modern maize breeding remain largely unexplored. This study systematically characterized lncRNA expression dynamics using transcriptome data from 137 maize inbred lines from different breeding eras in China. We identified 18,023 lncRNAs transcripts, grouped by expression trends across historical breeding eras. Comparative analysis revealed 2228 differentially expressed lncRNAs transcripts (DElncRNAs) between modern (CN2000&10s) and early (CN1960&70s) accessions. By integrating WGCNA and cis-target analysis, we identified candidate lncRNAs and putative lncRNA-PCG associations that may be associated with maize plant architecture-related processes. Further, 771 DElncRNAs were predicted to be associated with 810 protein-coding genes, and these associated genes were significantly enriched in plant hormone signal transduction. Dual-luciferase reporter assays provided preliminary experimental support that lncrna.33063 and lncrna.33068 can repress the promoter activity of ZmPIF5.2 in a heterologous transient expression system. Furthermore, we constructed a putative ceRNA-related candidate interaction network consisting of lncRNA–miRNA–mRNA triplets that include 317 candidate miRNA-lncRNA pairs and 8325 candidate miRNA-mRNA pairs, with the associated mRNAs enriched in biological processes such as morphogenesis, stimulus response, and hormone metabolism. These findings provide a set of candidate lncRNAs and lncRNA-PCG associations for future functional validation and may offer useful clues for understanding the possible roles of lncRNAs in agronomic trait-related biological processes and maize molecular breeding. Overall, this study provides candidate genetic resources and a framework for future investigation of lncRNA-associated relationships potentially related to agronomic trait variation in maize. Full article

Lauric acid is a characteristic component of Litsea cubeba seed oil, but FatB thioesterase candidates with predicted structural compatibility for C12 acyl-substrate accommodation remain insufficiently defined. In this study, seed oil content and fatty acid composition were examined during L. cubeba seed development. The fatty acid profile shifted from a C18:2-rich pattern at the early stage to a C12:0-dominated composition at later stages, providing the biochemical context for FatB candidate prioritization. Three FatB-like candidates were retrieved from a de novo seed transcriptome assembly and named LcFatB1, LcFatB2, and LcFatB3. Phylogenetic analysis, conserved motif comparison, sequence alignment, and homology modeling showed that LcFatB1 and LcFatB2 retained more complete FatB-like sequence and structural features than LcFatB3. S-dodecanoyl-4′-phosphopantetheine was used as a C12 acyl-4′-phosphopantetheine surrogate for molecular docking. Docking analysis indicated that LcFatB1 and LcFatB2 formed more interpretable C12-bound poses than LcFatB3. Subsequent 150 ns molecular dynamics simulations, free energy landscape analysis, residue–ligand interaction profiling, and catalytic tunnel analysis further distinguished the two main candidates. Compared with LcFatB2, LcFatB1 maintained a lower-displacement C12-bound state, a more compact contact environment involving Tyr116, Ser125, and Asn278, and a main tunnel with higher throughput and shorter length in the representative global-minimum conformation. LcFatB2 also retained the C12 surrogate but stabilized it in a distinct rearranged binding environment. These results support LcFatB1 as the strongest structurally prioritized FatB candidate among the three transcriptome-derived proteins, while LcFatB2 remains a plausible FatB-like candidate with a distinct C12-bound state. This prioritization provides computational structural clues for future biochemical testing but should not be interpreted as direct functional confirmation of FatB activity in vivo. Full article

Background: Endometrial cancer is a common gynecological malignancy, and elucidating its molecular basis may provide new clues for targeted intervention. This study investigated the role of ERBB3 in endometrial cancer cells and explored whether Ras-ERK/MAPK signaling is involved in ERBB3-mediated regulation. Methods: Bioinformatic screening was performed using public databases to identify candidate genes associated with endometrial cancer. ERBB3 was selected for further analysis. ERBB3 expression was evaluated in public datasets and examined in endometrial cancer cells. Loss-of-function experiments, rescue assays, Western blotting, and co-immunoprecipitation were used to assess the biological function and potential mechanism of ERBB3. Results: ERBB3 knockdown significantly inhibited proliferation, migration, and invasion, and promoted apoptosis in Ishikawa and RL95-2 cells. These changes were accompanied by decreased Ras-ERK/MAPK signaling. Moreover, Ras overexpression partially reversed the effects induced by ERBB3 knockdown. Co-immunoprecipitation suggested a molecular association between ERBB3 and Ras within a protein complex, but did not demonstrate direct physical binding. Conclusions: ERBB3 appears to promote malignant behaviors in endometrial cancer cells, and the Ras-ERK/MAPK pathway may be one of the downstream mechanisms involved. Further validation in additional experimental models and clinical samples is needed. Full article

Background: Alopecia areata (AA) is a common autoimmune alopecia disease. Evidence suggests that autophagy-related genes (ARGs) may contribute to its pathophysiology. This study aims to explore and identify potential autophagy-related biomarkers and molecular subtypes in AA. Methods: In this study, autophagy-related differential expression genes (ARDEGs) in AA were identified by comparing the differentially expressed genes (DEGs) in the GSE68801 dataset with the ARGs. Then, we applied three different machine learning methods to identify key hub genes and further verified them on independent datasets. We used the receiver operating characteristic (ROC) curve to evaluate the diagnostic potential of these hub genes and constructed a predictive nomogram. In addition, this study also used the consensus clustering method to define two AA subtypes and explored their immune characteristics and functional pathways through ssGSEA, MCPcounter and enrichment analysis. Experimental validation included qRT-PCR for four hub genes and Western blotting for critical autophagy markers. Results: Our analysis detected 10 ARDEGs in AA. Applying three machine learning algorithms, we identified four candidate hub genes, ATG9B, EIF4EBP1, WIPI1 and CCR2, and verified their expression patterns in independent cohorts. The combined four-gene model and nomogram showed potential diagnostic performance. Consensus cluster analysis divided AA cases into two subtypes, each associated with different immune infiltration and functional pathways. Downregulation of ATG9B and EIF4EBP1 and upregulation of CCR2 were verified by qRT-PCR. Western blotting further suggested altered autophagy-related protein expression in AA lesions, characterized by a reduced LC3B-II/I ratio and Beclin-1 expression and increased SQSTM1 expression. Conclusions: This study identified four candidate autophagy-related genes and two exploratory molecular subtypes in AA and may provide clues for understanding autophagy-related immune dysregulation and support further validation of candidate diagnostic markers. Full article

Antifungal killer toxins are cytotoxic proteins that have the potential to combat the growing threat of fungi to human health and agriculture. A lack of empirical tertiary structures has limited understanding of their mechanisms of action and their ability to target pathogens. In this study, AlphaFold and molecular dynamics simulations were used to generate tertiary structure models of all canonical Saccharomyces killer toxins and to place them in the context of historical empirical data. These models enabled the prediction of functional domains and posttranslational modifications, including proteolytic cleavage sites and disulfide bonds. They also revealed unexpected homology between Saccharomyces killer toxins, suggesting that all but K28 are likely ionophores. Structural homology to the well-studied killer toxins K1 and K2 enabled the prediction of the antifungal and immunity mechanisms of K1L, K21, K45, K74, and KHS. The understudied killer toxins Klus, KHR, and K62 were found to have homology to bacterial and plant toxins, including members of the aerolysin family and antifungal lectins. These structural similarities provide clues for the mechanisms of killer toxin carbohydrate binding, oligomerization, and membrane attack. This modeling approach will help guide the continued use of the model yeast S. cerevisiae to study killer toxins in the context of the wealth of functional data gathered in the decades since their first discovery. Full article

To identify candidate genes associated with skin tissue responses in Hu sheep raised under different regional rearing environments and to preliminarily explore their potential relevance to low-temperature-related environmental responses, this study used 1-year-old female Hu sheep raised in Anhui and Xinjiang as the experimental animals. Skin tissues were collected from the left scapular region, and their transcriptomic profiles were characterized by integrating histological analysis, RNA sequencing (RNA-seq), differential expression analysis, functional enrichment analysis, protein–protein interaction (PPI) network construction, and RT-qPCR validation. The results showed significant differences between the two groups in body weight, body length, body height, cannon circumference, rectal temperature, and ear temperature. Hematoxylin and eosin (H&E) staining indicated that the Xinjiang group exhibited a denser distribution of hair follicles, a relatively thicker dermis, and a more compact arrangement of collagen fibers, suggesting enhanced insulation-related skin characteristics. Transcriptome sequencing identified 295 differentially expressed genes (DEGs), including 193 upregulated and 102 downregulated genes. GO and KEGG enrichment analyses showed that these DEGs were mainly involved in immune and inflammatory responses, redox processes, extracellular matrix remodeling, and lipid and energy metabolism-related pathways, with significant enrichment in cytokine–cytokine receptor interaction, the chemokine signaling pathway, the NF-κB signaling pathway, glutathione metabolism, and drug metabolism–cytochrome P450. By further integrating PPI network analysis and functional annotation, CXCL13, CCL2, FGF21, GPX3, CYP1A1, HSD11B1, CDO1, and STEAP4 were identified as candidate genes. RT-qPCR results showed that the expression trends of the selected genes were generally consistent with the RNA-seq results. Overall, this study revealed differences in phenotypic traits, skin histological structure, and transcriptomic characteristics between Hu sheep raised in different regions, providing preliminary molecular clues potentially associated with low-temperature-related environmental responses. Given the differences in geographic origin and rearing environments between the two groups, the findings should be interpreted as associative evidence of skin transcriptomic responses in Hu sheep under different environmental conditions—rather than as direct causal evidence that low temperature alone drove these transcriptomic differences. Full article

Background/Objectives: Lung adenocarcinoma (LUAD) is molecularly heterogeneous and often requires rational drug combinations rather than single-agent therapy. Many computational repurposing methods use global signature matching or network scores, but they often treat dysregulated genes equally and optimize a single scalar objective. This study aimed to develop a contribution-aware computational framework for prioritizing repurposed multi-drug combinations that counteract LUAD driver modules; Methods: Ten LUAD driver scenarios were curated from the LUAD and non-small cell lung cancer literature and encoded as gene-level counteraction vectors across 44 unique genes. Direction-aware drug–gene interactions from the Comparative Toxicogenomics Database were processed into a weighted contribution matrix. A genetic algorithm was then used to search for small combinations of up to six drugs. The fitness function combined mean absolute error with terms for waste, mismatch, entropy, coverage, combination size, and optional cost. Orthogonal computational support was assessed using CLUE/Connectivity Map transcriptomic reversal analysis; Results: After filtering and optimization, 42 drugs and chemicals remained as candidate components across the scenarios. Increasing the combination size from one to three drugs usually reduced the mean absolute error, whereas larger combinations provided more limited gains. Compared with an MAE-only baseline, the full contribution-aware objective improved or preserved MAE in 54 of 60 scenario–drug-count comparisons. Drug and gene clustering identified interchangeable candidate groups and shared mechanisms across LUAD scenarios. CLUE-based analysis provided strong or moderate transcriptomic reversal support for several prioritized compounds; Conclusions: The proposed framework provides a transparent, scenario-based method for prioritizing repurposed drug combinations in LUAD. The results are computational and hypothesis-generating. They should guide future experimental testing, not clinical treatment decisions. Full article

Morbid obesity is a chronic condition characterized by metabolic disorders and low-grade chronic inflammation, both of which are closely linked to insulin resistance and adipokine dysregulation. In addition to its systemic effects, obesity also leads to structural and functional changes in the skin, supporting its role as an active metabolic and immunological organ. This study analyzed skin lesions occurring in individuals with morbid obesity and explored their potential relevance in the context of metabolic risk and treatment response rather than establishing clinically validated tools. The focus was on how excess adipose tissue affects the skin through metabolic, hormonal and mechanical mechanisms. Although this review focuses on morbid obesity, many of the included studies examine general obesity without separating its severity. Therefore, the findings may not fully reflect patients with BMI ≥ 40 kg/m² and should be interpreted with caution. Three main areas were considered: the pathophysiological mechanisms underlying obesity-related skin lesions, selected dermatological manifestations as potential markers associated with metabolic risk, and changes in these manifestations during pharmacological, surgical, and lifestyle interventions. Available studies show that acanthosis nigricans and multiple acrochordons are consistently associated with insulin resistance, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease. An increase in BMI is also associated with impairment of the epidermal barrier, changes in the composition of skin lipids, and modifications of the skin microbiome, while biomechanical factors promote the development of chronic inflammation in the intertriginous areas. It has been shown that normalization of metabolic parameters achieved through GLP-1-based pharmacotherapy, bariatric surgery, or lifestyle changes can improve some skin manifestations, especially acanthosis nigricans. However, it should be emphasized that most available data are based on cross-sectional or observational studies, and validated composite dermatological indices are still unavailable. Skin changes in patients with morbid obesity often reflect underlying metabolic and hormonal disturbances. They may have potential as additional, non-invasive clinical clues, but they should not be treated as independent tools for risk assessment or treatment monitoring. At present, most evidence shows associations only, and it is unclear whether these findings add meaningful predictive value beyond standard metabolic markers. More prospective studies are needed to confirm their clinical usefulness and to define their role in assessing metabolic risk and monitoring treatment over time. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease linked to epidermal barrier dysfunction, Th2-skewed immune polarization, and disrupted gut microbiota homeostasis. While probiotic interventions show promise in managing AD, the mechanisms governing strain-specific efficacy—particularly systemic modulation via the “gut–skin axis”—remaining to be fully elucidated. Methods: This study systematically compared the oral therapeutic effects of three Lacticaseibacillus rhamnosus strains (MG-A047, MG-A054, and LGG) in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Results: By integrating behavioral, histopathological, and serological assessments with 16S rRNA-based gut microbiota profiling and in vitro functional assays, this study offers a multidimensional evaluation of the strain-specific advantages and potential therapeutic mechanisms of three L. rhamnosus strains. The results demonstrate that MG-A054 most effectively alleviated cutaneous inflammation and pruritus, significantly reduced serum IgE and IL-4 levels, and attenuated epidermal hyperplasia and inflammatory cell infiltration (including mast cells and eosinophils). Mechanistically, this strain may directly inhibit hyaluronidase activity and mast cell degranulation, and specifically remodel the gut microbiota structure, thereby promoting a shift toward a healthier functional profile. Conclusions: These findings suggest that the superior efficacy of MG-A054 may be achieved through coordinated modulation of the gut–skin axis and related pathways. This study offers new mechanistic clues for understanding the strain-specific actions of probiotics and lays a preclinical foundation for the further development of MG-A054 as a potential targeted microecological therapy for AD. Full article

The craters on the moon hold important clues about the history of impacts in our solar system. To address the limitation of traditional intelligent methods in detecting buried craters, this study proposes a novel intelligent detection approach based on DEM and gravity data. We designed a hybrid network architecture (ResNet + ViT) that combines the local feature extraction strengths of Convolutional Neural Networks with the global context modeling capabilities of Vision Transformer. By combining the complementary information from DEM and gravity anomaly data, it achieves comprehensive detection of lunar craters—from those visible on the surface to buried subsurface structures. To mitigate the inherent sample imbalance in both gravity anomaly and DEM training data, we employ a U-Net architecture augmented with residual blocks and train it using a Focal Loss function with dynamic focusing parameters. Experimental results show that: (1) The proposed method attains high segmentation accuracy, achieving a mean Intersection over Union of 81.3% on the DEM test set and 82.6% on the gravity anomaly test set, respectively. (2) Our method outperforms U-Net and its mainstream variants, achieving a precision of 89.48% and superior detection completeness. (3) Application to representative geological units, including the Wugang Basin, Archimedes Crater, and Mare Moscoviense, validates the robustness and practical utility of our method. This study, thus, provides a novel technical framework for global-scale mapping of lunar impact craters and yields new insights into the evolutionary history of the lunar surface. Full article

Nephrocalcinosis, defined as the deposition of calcium salts within the renal parenchyma, represents a radiologic and pathologic endpoint shared by a broad spectrum of metabolic and monogenic disorders. Advances in genomic medicine have identified more than 30 genes involved in tubular transport, mineral and acid–base homeostasis, oxalate metabolism, mitochondrial function, ciliary signaling, and nephron development, reframing nephrocalcinosis as a heterogeneous manifestation of discrete molecular defects rather than a single disease entity. Despite this diversity, these conditions converge on common physicochemical pathways of tubular supersaturation, crystal nucleation, growth, and intrarenal retention. These processes are amplified by the intrinsic vulnerability of the renal medulla—characterized by hyperosmolality, hypoxia, and slow tubular flow—and by epithelial injury, loss of crystallization inhibitors, and impaired ciliary signaling. Distinct genotype–phenotype signatures, including age at onset, biochemical profiles, and extrarenal manifestations, provide important diagnostic clues and help differentiate major monogenic entities. The increasing availability of targeted gene panels, whole-exome sequencing, and whole-genome sequencing has substantially improved diagnostic yield, particularly in pediatric populations. Molecular diagnosis now directly informs therapeutic decision-making and long-term management, enabling a shift toward precision nephrology. This narrative review integrates genetic, mechanistic, and clinical perspectives to illustrate how molecular diagnosis reshapes the evaluation, prognosis, and treatment of nephrocalcinosis. Full article

The Wulonggou gold district is located on the northern margin of the Qinghai–Tibet Plateau and represents the most promising area for mineral exploration within the East Kunlun mineralized belt in Qinghai Province. Previous studies on this gold district have lacked a comprehensive assessment of its metal mineralization potential. This paper conducts a comprehensive investigation of the distribution patterns of geochemical data in the Wulonggou gold district, employing multivariate statistical analysis to explore the distribution characteristics of different geochemical elements. Based on the analysis of geochemical anomaly patterns, the median + 2MAD method and fractal method were further introduced to delineate geochemical anomalies. For comparison, machine learning methods—including the radial basis function link network (RBFLN) model and the Bayesian-optimized random forest (BO-RF) model—were also applied to generate different geochemical anomaly maps. By comparing the results obtained from each method, we found that the BO-RF model performed best in predicting geochemical anomalies. Based on the above information, the BO-RF model was integrated with geological background information to delineate prospective areas. These findings provide important clues for mineral exploration and development in the Wulonggou area and can serve as a reference for other regions with similar geological backgrounds. Full article

Background/Objectives: High-altitude pulmonary edema (HAPE) remains a serious condition with limited preventive options. This study evaluated the prophylactic protective effects of nebulized human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in a rat model of hypobaric hypoxia-induced lung injury and explored potential mechanistic clues, with a focus on oxidative stress and TEK/Tie2 signaling. Methods: Rats were exposed to hypobaric hypoxia (47 kPa; 9.7% O₂) for 72 h and received prophylactic nebulized hUC-MSC-EVs (300 μg/rat). Lung injury was evaluated by histopathology, wet-to-dry ratio, and bronchoalveolar lavage fluid (BALF) protein concentration. Invasive pulmonary function indices were measured using a forced oscillation system. BALF cytokines (TNF-α, IL-6, and IL-10), reactive oxygen species (ROS), and TEK/Tie2 expression in lung tissue were assessed. In addition, transcriptome sequencing (RNA-seq) was performed to characterize global transcriptional changes. N-acetylcysteine (NAC), a classical antioxidant, was included as an auxiliary mechanistic intervention to assess the association of ROS with TEK/Tie2 changes. Results: Compared with hypoxia controls, prophylactic nebulized hUC-MSC-EVs reduced histopathological injury, pulmonary edema, and barrier leakage, and improved pulmonary function indices. hUC-MSC-EV intervention also attenuated inflammatory responses in BALF, with decreased TNF-α and IL-6 and increased IL-10. Hypobaric hypoxia increased ROS accumulation and decreased TEK/Tie2 expression, whereas nebulized hUC-MSC-EVs reduced ROS and partially preserved TEK/Tie2 expression. NAC pretreatment similarly reduced ROS and was accompanied by Tie2 preservation. Conclusions: Prophylactic nebulized hUC-MSC-EVs mitigated hypobaric hypoxia-induced lung injury, accompanied by reduced oxidative stress, improved vascular barrier integrity, and preservation of TEK/Tie2 expression. These findings support nebulized hUC-MSC-EVs as a potential lung-targeted prophylactic strategy for hypobaric hypoxia-induced lung injury and suggest that ROS imbalance may be associated with Tie2 preservation. Full article